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  • 1
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-04-19)
    Abstract: Glioblastoma (GBM) patients present poor prognosis. Deubiquitination by deubiquitinating enzymes (DUBs) is a critical process in cancer progression. Ubiquitin-specific proteases (USPs) constitute the largest sub-family of DUBs. Evaluate the role of USP32 in GBM progression and provide a potential target for GBM treatment. Clinical significance of USP32 was investigated using Gene Expression Omnibus databases. Effects of USP32 on cell growth and metastasis were studied in vitro and in vivo. Differentially expressive genes between USP32-knockdown U-87 MG cells and negative control cells were detected using RNA sequencing and used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomic pathway enrichment analyses. Finally, RT-qPCR was used to validate the divergent expression of genes involved in the enriched pathways. USP32 was upregulated in GBM patients, being correlated to poor prognosis. USP32 downregulation inhibited cell growth and metastasis in vitro. Furthermore, USP32 knockdown inhibited tumorigenesis in vivo. In addition, UPS32 was identified as a crucial regulator in different pathways including cell cycle, cellular senescence, DNA replication, base excision repair, and mismatch repair pathways. USP32 acts as an oncogene in GBM through regulating several biological processes/pathways. It could be a potential target for GBM treatment.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 2
    In: World Neurosurgery, Elsevier BV, ( 2023-10)
    Type of Medium: Online Resource
    ISSN: 1878-8750
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2530041-6
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  • 3
    In: CNS Neuroscience & Therapeutics, Wiley
    Abstract: Glioblastoma (GBM) has been reported to be the most common high‐grade primary malignant brain tumor in clinical practice and has a poor prognosis. O 6 ‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation has been related to prolonged overall survival (OS) in GBM patients after temozolomide treatment. Methods Proteomics and metabolomics were combined to explore the dysregulated metabolites and possible protein expression alterations in white matter (control group), MGMT promoter unmethylated GBM (GBM group) or MGMT promoter methylation positive GBM (MGMT group). Results In total, 2745 upregulated and 969 downregulated proteins were identified in the GBM group compared to the control group, and 131 upregulated and 299 downregulated proteins were identified in the MGMT group compared to the GBM group. Furthermore, 131 upregulated and 299 downregulated metabolites were identified in the GBM group compared to the control group, and 187 upregulated and 147 downregulated metabolites were identified in the MGMT group compared to the GBM group. The results showed that 94 upregulated and 19 downregulated proteins and 20 upregulated and 16 downregulated metabolites in the MGMT group were associated with DNA repair. KEGG pathway enrichment analysis illustrated that the dysregulated proteins and metabolites were involved in multiple metabolic pathways, including the synthesis and degradation of ketone bodies, amino sugar and nucleotide sugar metabolism. Moreover, integrated metabolomics and proteomics analysis was performed, and six key proteins were identified in the MGMT group and GBM group. Three key pathways were recognized as potential biomarkers for recognizing MGMT promoter unmethylated GBM and MGMT promoter methylation positive GBM from GBM patient samples, with areas under the curve of 0.7895, 0.7326 and 0.7026, respectively. Conclusion This study provides novel mechanisms to understand methylation in GBM and identifies some biomarkers for the prognosis of two different GBM types, MGMT promoter unmethylated or methylated GBM, by using metabolomics and proteomics analyses.
    Type of Medium: Online Resource
    ISSN: 1755-5930 , 1755-5949
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2423467-9
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  • 4
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 13 ( 2021-8-16)
    Abstract: Background and Aims: It has recently emerged the concept of “obesity paradox,” a term used to describe an inverse association between obesity and clinical outcomes in cardiovascular diseases and stroke. The purpose of this study was to investigate the association between body mass index (BMI) and the risk of intracranial aneurysm rupture. Methods: In this study, we conducted a retrospective analysis of a prospectively maintained database of patients with intracranial aneurysms from 21 medical centers in China. A total of 3,965 patients with 4,632 saccular intracranial aneurysms were enrolled. Patients were separated into unruptured ( n = 1,977) and ruptured groups ( n = 1,988). Univariable and multivariable logistic regression analyses were performed to determine the association between BMI and intracranial aneurysm rupture. Results: Compared to the patients with normal BMI (18.5 to & lt; 24.0 kg/m 2 ), the odds of intracranial aneurysm rupture were significantly lower in patients with BMI 24.0 to & lt; 28.0 kg/m 2 (OR = 0.745, 95% CI = 0.638–0.868, P = 0.000) and patients with BMI ≥ 28.0 kg/m 2 (OR = 0.628, 95% CI = 0.443–0.890, P = 0.009). Low BMI ( & lt;18.0 kg/m 2 ) was not associated with intracranial aneurysm rupture (OR = 0.894, 95% CI = 0.483–1.657, P = 0.505). For males, both the BMI 24.0 to & lt; 28.0 kg/m 2 (OR = 0.606, 95% CI = 0.469–0.784, P = 0.000) and the BMI ≥ 28.0 kg/m 2 (OR = 0.384, 95% CI = 0.224–0.658, P = 0.001) were associated with a lower rupture risk, whereas the inverse association was not observed in females. Both the BMI 24.0 to & lt; 28.0 kg/m 2 (OR = 0.722 for aged 50–60y, 95% CI = 0.554–0.938, P = 0.015; OR = 0.737 for aged & gt;60y, 95% CI = 0.586–0.928, P = 0.009) and the BMI ≥ 28.0 kg/m 2 (OR = 0.517 for aged 50–60y, 95% CI = 0.281–0.950, P = 0.0034; OR = 0.535 for aged & gt;60y, 95% CI = 0.318–0.899, P = 0.0018) was associated with a lower rupture risk in patients aged ≥50 years, whereas the association was not significant in patients aged & lt;50 years. Conclusions: Increased BMI is significantly and inversely associated with saccular intracranial aneurysm rupture in males and patients aged ≥50 years.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2558898-9
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  • 5
    In: Cell Death & Disease, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-01-09)
    Abstract: Glioblastoma multiforme (GBM) is the most lethal primary brain tumor with a poor median survival of less than 15 months. However, clinical strategies and effective therapies are limited. Here, we found that the second-generation small molecule multi-CDK inhibitor AT7519 is a potential drug for GBM treatment according to high-throughput screening via the Approved Drug Library and Clinical Compound Library (2718 compounds). We found that AT7519 significantly inhibited the cell viability and proliferation of U87MG, U251, and patient-derived primary GBM cells in a dose-dependent manner. Furthermore, AT7519 also inhibited the phosphorylation of CDK1/2 and arrested the cell cycle at the G1-S and G2-M phases. More importantly, AT7519 induced intrinsic apoptosis and pyroptosis via caspase-3-mediated cleavage of gasdermin E (GSDME). In the glioblastoma intracranial and subcutaneous xenograft assays, tumor volume was significantly reduced after treatment with AT7519. In summary, AT7519 induces cell death through multiple pathways and inhibits glioblastoma growth, indicating that AT7519 is a potential chemical available for GBM treatment.
    Type of Medium: Online Resource
    ISSN: 2041-4889
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2541626-1
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  • 6
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 15 ( 2021-11-26)
    Abstract: As a non-invasive, low-cost medical imaging technology, magnetic resonance imaging (MRI) has become an important tool for brain tumor diagnosis. Many scholars have carried out some related researches on MRI brain tumor segmentation based on deep convolutional neural networks, and have achieved good performance. However, due to the large spatial and structural variability of brain tumors and low image contrast, the segmentation of MRI brain tumors is challenging. Deep convolutional neural networks often lead to the loss of low-level details as the network structure deepens, and they cannot effectively utilize the multi-scale feature information. Therefore, a deep convolutional neural network with a multi-scale attention feature fusion module (MAFF-ResUNet) is proposed to address them. The MAFF-ResUNet consists of a U-Net with residual connections and a MAFF module. The combination of residual connections and skip connections fully retain low-level detailed information and improve the global feature extraction capability of the encoding block. Besides, the MAFF module selectively extracts useful information from the multi-scale hybrid feature map based on the attention mechanism to optimize the features of each layer and makes full use of the complementary feature information of different scales. The experimental results on the BraTs 2019 MRI dataset show that the MAFF-ResUNet can learn the edge structure of brain tumors better and achieve high accuracy.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2411902-7
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